Retinoic acid (RA) enhanced the binding of 125I-labelede pidermal growth factor (EGF) to various fibroblastic and epidermal cell lines by increasing the number of receptor sites available for binding. This effect is specific for EGF-receptors and is not the result of increased internalization and/or degradation of EGF. Rate of restoration of EGF-receptor binding after "down regulation" by excess EGF is faster in RA-treated cells, suggesting that RA stimulates the synthesis of this cell surface receptor. At the same time RA decreases growth rates of a variety of cell lines. Soft agar colony formation by 3T3 A31-1-BP-2 cells is decreased by RA and increased by the tumor promoter TPA. RA and retinol prevented colony formation in the presence or absence of TPA. Exceptionally, the fibroblastic rat kidney cell line NRK 536-3 (SA6) responded to RA by a remarkable increase in colony forming ability in soft agar medium, but only when given to the cells in the presence of sarcoma growth factor. RA by itself had no activity. RA increased, whereas TPA decreased, the biosynthesis of secreted procollagen in 3T6 fibroblasts and in 3T3 A31-1-BP-2.